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Novel targeted pH-responsive drug delivery systems based on PEGMA-modified bimetallic Prussian blue analogs for breast cancer chemotherapy

The development of novel nanoparticle-based drug delivery systems (nano-DDSs) with high loading capacity, low toxicity, precise targeting, and excellent biocompatibility remains urgent and important for the treatment of breast cancer (BC). Herein, novel BC-targeted nano-DDSs based on bimetallic Prus...

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Detalles Bibliográficos
Autores principales: Chen, Qiang, Huang, Xiaoyu, Zhang, Geyi, Li, Jiangnan, Liu, Yang, Yan, Xu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9828049/
https://www.ncbi.nlm.nih.gov/pubmed/36712642
http://dx.doi.org/10.1039/d2ra06631a
Descripción
Sumario:The development of novel nanoparticle-based drug delivery systems (nano-DDSs) with high loading capacity, low toxicity, precise targeting, and excellent biocompatibility remains urgent and important for the treatment of breast cancer (BC). Herein, novel BC-targeted nano-DDSs based on bimetallic Prussian blue analogs (PBA-DDSs) for intracellular doxorubicin (DOX) delivery and pH-responsive release were developed. Two kinds of bimetallic PBA, namely CuFe (copper–iron) PBA and CoFe (cobalt–iron) PBA, were synthesized by a coprecipitation method, followed by modification with polyethyleneglycol methacrylate (PEGMA) via surface-initiated atom transfer radical polymerization and immobilization with the AS1411 aptamer to obtain two kinds of novel BC-targeted nano-DDS. CuFePBA@PEGMA@AS1411 and CoFePBA@PEGMA@AS1411 showed high drug loading efficiency of 80% and 84%, respectively, for DOX, while 56.0% and 75.9% DOX release could be achieved under acidic pH conditions. In vitro cell viability and in vivo experiments proved the good biocompatibility of both PBA-DDSs. Cellular uptake and in vivo distribution suggested that both PBA-DDSs had efficient nucleolin-targeting capability, indicating the targeted delivery of DOX in tumor tissues. In vivo evaluation of anti-BC efficacy further confirmed that the obtained PBA-DDSs exhibited excellent therapeutic efficacy with limited side-effects. Therefore, the proposed novel PBA-DDSs can be used as secure and effective drug nano-DDSs for BC chemotherapy.